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Major depressive disorder (MDD) is increasingly considered as a multifactorial neuropsychiatric disease involving dysregulation over multiple neurotransmitter systems. This chapter examines the complex role of serotonin, dopamine, and glutamate receptors in the pathophysiology of MDD, with a focus on their contributions to emotional regulation, reward processing, and synaptic plasticity. Recent evidence from pharmacological, genetic, and neuroimaging studies highlighted the involvement of receptor subtypes—such as 5-HT1A, 5-HT1A/C, D1–D3, and both ionotropic and metabotropic glutamate receptors—in mediating depressive symptoms and therapeutic responses. This chapter will point out potential targets for innovative and rapid-acting antidepressant strategies, emphasizing the need for personalized treatment approaches in MDD.

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The Complex Role of Serotonin–Dopamine–Glutamate Receptors in Major Depression

  • 章节

  • 发表日期：

    2026年

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  • Laura Orsolini,
  • Giulio Longo,
  • Michele Giordano,
  • Umberto Volpe

摘要

Major depressive disorder (MDD) is increasingly considered as a multifactorial neuropsychiatric disease involving dysregulation over multiple neurotransmitter systems. This chapter examines the complex role of serotonin, dopamine, and glutamate receptors in the pathophysiology of MDD, with a focus on their contributions to emotional regulation, reward processing, and synaptic plasticity. Recent evidence from pharmacological, genetic, and neuroimaging studies highlighted the involvement of receptor subtypes—such as 5-HT1A, 5-HT1A/C, D1–D3, and both ionotropic and metabotropic glutamate receptors—in mediating depressive symptoms and therapeutic responses. This chapter will point out potential targets for innovative and rapid-acting antidepressant strategies, emphasizing the need for personalized treatment approaches in MDD.